The long term objective of this work is to quantify uptake of high energy radionuclides such as I-131. Quantification of I-131 for internal dosimetry has gained renewed interest due to the recent success of radioimmunotherapy (RIT) in treating B-cell non-Hodgkin's lymphoma here at the University of Michigan and at other institutions. The latest data from the phase II RIT trial using I-131 labeled anti-B1 MoAb at this university shows the response rate to be 100 percent, with 71 percent of the responses being complete. We propose the use of Monte Carlo simulation for developing accurate SPECT quantification of I-131. A verified, fast, versatile Monte Carlo code suitable for simulating SPECT imaging of higher energy photon emitters is not presently available. We will carry out extensive verification tests to establish such a code which will then be applied to assess and solve significant problems in quantification such as scatter, penetration, attenuation and effects of object shape, size and background activity. We propose to build on the existing SIMIND and SKEPTIC Monte Carlo codes that are well established for low energy photons, and which have recently been expanded to include collimator scatter and penetration which is essential for accurate modeling of higher energy photons. Preliminary data comparing I-131 simulation results of SIMIND and SKEPTIC with measurements for simple geometries appear promising but their accuracy in modeling realistic imaging situations will be tested by the proposed research. The codes will also be verified for positron SPECT (511 keV photons) which is gaining interest as a low cost alternative to PET. We will improve and expand the two codes to include realistic simulation or backscatter photons, exact modeling of collimator hole shape and effects such as Doppler broadening. The more promising of the two codes will be parallelized in order to achieve significant speed-up, which is especially important when simulating tomographic acquisitions. Scatter- penetration correction is a pre-requisite for accurate quantification, and a main aspect of the present work will be Monte Carlo evaluation of scatter and collimator penetration in I-131 SPECT and assessment of compensation techniques that are based on spectral analysis. Fulfilling all aims of the proposed work will allow for accurate quantification which is necessary to predict response to therapy and for determining maximum activity to be administered. Apart from quantification, this work will have applications in the design of future imaging systems for high energy photons.